Abstract A novel, biologically inspired strategy will be used to improve preservation of mesenchymal stem cells (MSCs). MSCs are being investigated for the treatment of cardiovascular disorders, diabetes, connective tissue disorders, acute lung injury, amyotrophic lateral sclerosis, kidney diseases and more. The proposed investigation addresses a critical obstacle for widespread use of MSCs: a high quality, consistent preservation protocol. We believe that multicomponent solutions can preserve MSCs effectively. Testing that hypothesis using conventional methods could require up to ~7,000 experiments, which is clearly not practical. We have developed a computational algorithm that accelerates optimization and reduces the experimentation required. We propose to develop in Aim #1, several candidate preservation solutions using naturally- occurirng molecules that are biocompatible. Preliminary studies demonstrate that there is a `sweet spot' where the molecules of interest act in concert to improve the survival of cells. Outside of that range, the relationship amongst the molecules can actually be detrimental. The proposed investigation uses a variety of spectroscopic techniques to characterizing the potential molecular mechanisms for the protection afforded by the multi-component solutions in Aim #2. Finally, induced pluripotent stem (iPS) cells are another biological system of tremendous interest. We propose to apply the approach developed for MSCs to iPS colonies of cells and improve preservation of this important cell type in Aim #3. The proposed investigation has the potential to transform cell preservation by moving away from DMSO to biocompatible, naturally occurring molecules. Streamline processing protocols by eliminating introduction and washing steps. Enable development of fit-for-purpose preservation protocols that can vary with cell type and even application to application through the use of algorithm-driven protocol optimization.